This is one of three interrelated applications for financial support to plan multiprotocol clinical-epidemiologic research in retinopathy of prematurity (ROP). Retinopathy of Prematurity (ROP) remains a serious public health problem causing significant visual sequelae in an estimated 3400 premature survivors per year in the United States, despite the now recognized use of Cryotherapy. Case control studies among infants, older reports of successful treatment of ROP with oxygen and studies conducted in an animal model demonstrate that chronic (weeks-long) hypoxia (PaO2=38) during the ROP healing may be a critical factor in differentiating ROP that progresses from ROP that regresses, an hypothesis supported by the association of retinopathy with retinal hypoxia in other proliferative retinopathies, such as diabetic retinopathy. The animal model retinopathy benefits from increased therapeutic oxygen, administered during the active period of disease. These data justify the testing of the hypothesis that "Supplemental Oxygen Treatment of Prethreshold ROP (STOP-ROP) will result in a reduction by at least one third in the number of infants with one or two eyes progressing to Threshold ROP." Infants who develop Prethreshold ROP (as defined in the CRYO-ROP study) will receive continuous transcutaneous oxygen saturation monitoring and be randomly assigned oxygen administration at one of two specified oxygen levels, standard vs increased. Their ROP status will be determined prospectively, and the outcome variable will be the number of infants who progress to Threshold ROP for cryotherapy by 3 months after their expected date of full term delivery. The projected sample sizes are compatible with a 2-3 year enrollment using 15-25 centers, and the study is planned to involve coordinated efforts for data management, budget, personnel, study forms and the Data and Safety Monitoring Committee with two other complimentary studies of 1) light reduction to prevent ROP (LIGHT-ROP) and 2) minimal intervention in Threshold ROP (MINI-ROP).